For proper immunosurveillance, lymphocytes need to recirculate continuously between blood and tissues to patrol the body. Naïve lymphocytes mainly migrate to organized secondary lymphoid tissues, such as lymph nodes, whereas activated effector lymphocytes can also leave blood at peripheral tissues. Lymphocytes emigrate from blood by interacting with endothelial cells. They use a sequential cascade that involves tethering, rolling, activation, firm adhesion, crawling, and transmigration. At the molecular level, selectins, chemokine receptors, and integrins on the lymphocyte surface play key roles during the different steps of this extravasation cascade. In some diseases, lymphocyte trafficking can be either insufficient (e.g., immunodeficiencies, cancer) or exaggerated (e.g., autoimmune and other inflammatory diseases). Monoclonal antibodies against α4 integrin (natalizumab) and α4β7 integrin (vedolizumab), and a small-molecule antagonist of sphingosine-1-phosphate receptor (fingolimod), all of which inhibit lymphocyte trafficking through different mechanisms, are used in the clinics for the treatment of inflammatory diseases. © 2023 Elsevier Ltd. All rights reserved.

Endothelium; lymphatics; lymphocytes; migration; vasculature